A filtration membrane useful for protein separations is a synthetic (frequently polymeric) selective barrier for industrial or lab-scale microfiltration (MF) or ultrafitration (UF) (see Leos J. Zeman and Andrew L. Zydney, “Microfiltration and Ultrafiltration: Principles and Applications,” 1996, Marcel Dekker, Inc., p. 3). In these processes, certain feed stream components, such as proteins, pass through pores of the membrane into a filtrate, while other, usually larger, proteins or components are retained by the membrane in the retentate (see Zeman and Zydney, supra, p. 3).
Protein ultrafiltration is a pressure-driven membrane process used for the concentration or purification of protein solutions (Robert van Reis and Andrew L. Zydney, “Protein Ultrafiltration” in Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis, and Bioseparation, M. C. Flickinger and S. W. Drew, eds., John Wiley & Sons, Inc. (1999), p. 2197). UF membranes typically have a mean pore size between 10 and 500 Angstroms, which is between the mean pore size of reverse osmosis and microfiltration membranes. Ultrafiltration separates solutes based on differences in the rate of filtration of different components across the membrane in response to a given pressure driving force (R. van Reis and A. L. Zydney, supra, p. 2197). Solute filtration rates, and thus membrane selectivity, are determined by both thermodynamic and hydrodynamic interactions (R. van Reis and A. L. Zydney, supra, p. 2197). Ultrafiltration is frequently used in downstream processing for protein concentration, buffer exchange and desalting, protein purification, virus clearance, and clarification (R. van Reis and A. L. Zydney, supra, p. 2197).
Protein purification is also accomplished using high-performance tangential flow filtration (HPTFF), with the desired protein collected in either the retentate or filtrate depending on the relative filtration rates (R. van Reis and A. L. Zydney, supra, p. 2197). HPTFF is useful for separating proteins of similar size using semipermeable membranes (See, for example, R. van Reis, et al., Biotech. Bioeng. 56:71–82 (1997) and R. van Reis et al., J. Memb. Sci. 159:133–142 (1999)). HPTFF achieves high selectivity by controlling filtrate flux and device fluid mechanics in order to minimize fouling and exploit the effects of concentration polarization (R. van Reis et al., J. Memb. Sci. 159:133–142 (1999)).
Despite the value of these advanced filtration methods, there is a need for improved filtration membrane characteristics such that separation speed may be increased without sacrificing membrane selectivity or speed. Such improvements would reduce cost of separation and increase yield of valuable proteins.